HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Human Apolipoprotein D: an Unusual Lipocalin Structure

Human apolipoprotein D (ApoD) is a plasma glycoprotein that associates with high density lipoprotein (HDL). ApoD has been shown to bind to progesterone and arachidonic acid and plays a possible role in cancer development and neurological diseases. In this Paper of the Week, Andreas Eichinger and colleagues determined the crystal structure of free ApoD and ApoD in complex with progesterone.

Crystal structure of free ApoD (yellow) and ApoD in complex with progesterone (red).

The crystal structure reveals an eight-stranded antiparallel -barrel that is typical of the lipocalin protein family. However, ApoD also exhibits distinct features that have not been observed in other lipocalins. First, ApoD possesses a narrow, mainly uncharged pocket that can accommodate two large hydrophobic ligands that are chemically unrelated: progesterone and arachidonic acid. Second, three of the loops at the entrance to the protein's ligand-binding site contain several solvent-exposed hydrophobic side chains that could act as molecular protrusions that insert into the lipid phase of the HDL. The solution of this structure is important clinically because of the well established correlation between cholesterol levels and cardiovascular disease.

FOOTNOTES

See referenced article, J. Biol. Chem. 2007, 282, 31068-31075

[More Papers of the Week]